Molecular study of six families originating from the Middle-East and presenting with autosomal recessive osteopetrosis

Eur J Med Genet. 2007 May-Jun;50(3):188-99. doi: 10.1016/j.ejmg.2007.01.005. Epub 2007 Feb 21.


Autosomal recessive osteopetrosis is a severe hereditary bone disease whose cellular basis is in the osteoclast, but with heterogeneous molecular defects. We hereby report the clinical and the molecular study of seven patients affected by the recessive form of osteopetrosis (ARO) from six families originating from the Middle-East: four from Lebanon and two from Syria. Parental consanguinity was found in five families. The mean age of diagnosis was 3 months. Failure to thrive, prominent forehead, exophthalmia, optic atrophy, hepatosplenomegaly, neurological manifestations, anaemia, thrombocytopenia, hypocalcaemia, elevated hepatic enzymes and acid phosphatase, and an early fatal outcome were common. Macrocephaly, strabismus, and brain malformations were relatively less common. Mutations were identified in two genes: TCIRG1 and OSTM1. Phenotype-genotype correlation is discussed.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Consanguinity
  • DNA Mutational Analysis
  • DNA Primers / genetics
  • Exons
  • Female
  • Genes, Recessive
  • Genotype
  • Humans
  • Infant
  • Lebanon
  • Male
  • Membrane Proteins / genetics
  • Mutation
  • Osteopetrosis / enzymology
  • Osteopetrosis / genetics*
  • Pedigree
  • Phenotype
  • RNA Splicing / genetics
  • Syria
  • Ubiquitin-Protein Ligases / genetics
  • Vacuolar Proton-Translocating ATPases / genetics


  • DNA Primers
  • Membrane Proteins
  • OSTM1 protein, human
  • TCIRG1 protein, human
  • Ubiquitin-Protein Ligases
  • Vacuolar Proton-Translocating ATPases